P1040: HIGHER ESTIMATED PLASMA VOLUME STATUS IS ASSOCIATED WITH INCREASED THROMBOTIC RISK AND IMPAIRED SURVIVAL IN PATIENTS WITH PRIMARY MYELOFIBROSIS
Authors: M. Lucijanic, I. Krecak, E. Soric, D. Galusic, H. Holik, V. Perisa, M. Moric Peric, I. Zekanovic, R. Kusec
Journal: HemaSphere (2022)

Background: Blood plasma experiences substantial changes in both volume and composition in patients with chronic myeloproliferative neoplasms (MPN) and represents large reservoir of cytokines and other mediators of inflammation. Higher estimated plasma volume status (ePVS) has been shown to correlate with increased thrombotic risk in polycythemia vera patients, but its clinical and prognostic associations are unknown in patients with other MPN subsets. Aims: To estimate clinical and prognostic associations of ePVS in patients with primary myelofibrosis (PMF). Methods: We retrospectively analyzed a cohort of 167 patients with myelofibrosis treated in 6 Croatian hematology centers in period from 2004-2021. Diagnosis was established according to the WHO 2016 criteria. ePVS was calculated using the Strauss derived Duarte formula: 100-hematocrit (%)/hemoglobin (g/dL) and expressed as dl/g. ePVS associations with baseline clinical parameters and its prognostic associations with overall survival (OS), time to thrombosis (TTT) and time to bleeding (TTB) were analyzed. Results: There were 167 patients with PMF analyzed (72 pre-fibrotic and 95 overt fibrotic). Median age was 68 years, there were 65% males, 67% were JAK2 mutated. Intermediate-2 or high DIPSS risk was present in 48% of patients. Median ePVS was 5.62 dl/g. Higher ePVS was significantly associated with higher degree of bone marrow fibrosis, absence of JAK2 mutation, presence of constitutional symptoms, presence of circulating blasts, transfusion dependency, larger palpable spleen size, higher Charlson comorbidity index, history of bleeding, lower WBC, lower platelet count, lower hemoglobin, higher RDW, higher LDH, higher CRP, higher ferritin, lower albumin, higher fibrinogen, higher risk DIPSS status (P<0.05 for all analyses). Median follow-up of our cohort was 57 months. During follow-up period a total of 79 patients died, 18 experienced thrombotic event (14 arterial and 5 venous thromboses) and 14 experienced bleeding event. Higher ePVS stratified at the ROC curve analysis defined cut-off points was significantly associated with worse OS (ePVS>6.2 dl/g, HR 1.74, P=0.017) and shorter TTT (ePVS>6.6 dl/g, HR 2.69, P=0.047) as shown in Figure. There was no significant association with TTB. In a multivariate Cox regression analysis model association of higher ePVS with increased thrombotic risk (HR 3.22, P=0.019) was present independently of WBC (HR 1.02, P=0.003), whereas JAK2 mutational status (HR 2.74, P=0.080) and cardiovascular risk factors (HR 7.12, P=0.060) retained marginal significance. Association with OS diminished in multivariate analysis after adjustment for DIPSS. Image:Summary/Conclusion: PMF patients with more advanced disease features (more pronounced cytopenias and splenomegaly) have higher ePVS indicative of expanded plasma volume. Higher ePVS is associated with higher thrombotic risk and impaired survival.